Development and Commercial Launch of Genetic and Advanced Tests

「As a new contract-testing service in the infectious disease field, we began offering a new screening test in March 2026 for 14 high-risk human papillomavirus (HPV) genotypes. The test classifies them into six individual genotypes—types 16, 18, 31, 45, 51, and 52—and three groups—types 33/58, 35/39/68, and 56/59/66. It is eligible for insurance reimbursement of 347 points, is useful for diagnosing and assessing the risk of high-risk HPV infection, and can contribute to improving the quality of cervical cancer screening.」

「高リスク型ヒトパピローマウイルス（HPV）14種類（遺伝子型）を対象として6つの遺伝子型および３つのグループに分別する新しいスクリーニング検査を2026年３月より開始しました。」

「The main new contract-testing services launched during the fiscal year include three insurance-covered tests useful for determining treatment strategies for malignant tumors and hereditary diseases. In June 2025, we began offering colorectal cancer methylation detection on a contract basis. Treatment guidelines indicate that determining DNA methylation status in colorectal cancer is useful in assisting the selection of anti-EGFR antibodies for first-line treatment of advanced or recurrent colorectal cancer and for patients previously treated. This test detects methylation in 16 regions reflecting genome-wide DNA methylation status and is eligible for insurance reimbursement of 2,500 points. In September of the same year, we began offering IDH1 gene mutation analysis on a contract basis. Mutations in isocitrate dehydrogenase 1 (IDH1) can cause the overproduction of substances involved in DNA and histone methylation, potentially promoting the progression of acute myeloid leukemia (AML). The test is useful as a companion test for determining eligibility for ivosidenib (brand name: Tibsovo), a newly launched selective inhibitor for mutant IDH1 in AML, and is eligible for insurance reimbursement of 2,500 points. Also in the same month, we began offering concizumab quantification testing on a contract basis. Concizumab (brand name: Alhemo subcutaneous injection) is an anti-TFPI (tissue factor pathway inhibitor) monoclonal antibody used to treat congenital hemophilia. Measuring plasma concizumab concentrations is useful for dose adjustment in patients with congenital hemophilia receiving concizumab, and in vitro diagnostic reagents became eligible for insurance coverage of 12,850 points.」

「As a result of research and development activity during the consolidated fiscal year, in the field of genetic testing, we began offering tests for eight syndromic hearing-loss conditions eligible for insurance coverage on a contract basis from September 2024 as an expansion of our congenital hearing-loss testing.」

「As a research and development achievement during the interim consolidated accounting period, following the launch in March 2024 of contract testing for the syndromic hearing-loss conditions Usher syndrome and branchio-oto-renal syndrome as new congenital hearing-loss tests, we began offering genetic testing eligible for insurance coverage in September for six conditions: Epstein syndrome, Wolfram syndrome, Alport syndrome, cryopyrin-associated periodic syndrome, CHARGE syndrome, and Jervell and Lange-Nielsen syndrome (JLNS), a form of congenital long QT syndrome. This work is conducted through technical collaboration with the Department of Artificial Hearing at the School of Medicine, Shinshu University (Specially Appointed Professor Shinichi Usami (宇佐美真一)).」

「As new tests for congenital hearing loss, we began offering NGS panel analysis for the syndromic hearing-loss conditions Usher syndrome and branchio-oto-renal syndrome on a contract basis from March 2024. These tests are conducted through technical collaboration with the Department of Artificial Hearing at the School of Medicine, Shinshu University (Specially Appointed Professor Shinichi Usami (宇佐美真一)), and both are eligible for insurance coverage of 5,000 points as genetic testing. Finally, in addition to our existing genetic testing for familial hypercholesterolemia (FH), we independently developed an NGS panel for lipid disorders covering five diseases—abetalipoproteinemia, familial hypobetalipoproteinemia type 1 (homozygous), primary hyperchylomicronemia, and Tangier disease—and began offering it on a contract basis from May 2024.」

「As a research and development achievement during the first nine months of the fiscal year, we began offering testing for hereditary connective tissue diseases (HCTD) using NGS panel analysis on a contract basis from May 2023. The test is conducted through technical collaboration with the Genetic Medicine Research Center at Shinshu University Hospital (Director Tomoki Furusho (古庄知己)).」

「As a research and development achievement during the first nine months of the fiscal year, we began offering testing for hereditary connective tissue diseases (HCTD) using NGS panel analysis on a contract basis from May 2023. The test is conducted through technical collaboration with the Genetic Medicine Research Center at Shinshu University Hospital (Director Tomoki Furusho (古庄知己)). It also performs panel analysis of the three causal genes for Osler disease (hereditary hemorrhagic telangiectasia), mutations in the type I collagen genes COL1A1 and COL1A2, which are causal genes in more than 90% of osteogenesis imperfecta cases, and 13 causal genes other than type I collagen, as related differential diagnoses. Analysis of genes considered causal for these diseases is eligible for insurance reimbursement of either 8,000 or 5,000 points as genetic testing (D006-4).」

「As a research and development achievement during the first six months of the fiscal year, we began offering testing for hereditary connective tissue diseases (HCTD) using NGS panel analysis on a contract basis from May 2023.」

「Through collaboration with the Department of Artificial Hearing at the School of Medicine, Shinshu University, we upgraded the genetic mutation test for congenital hearing loss from a detection panel covering 154 mutations in 19 genes to one covering 1,135 mutations in 50 genes. Following this, in response to revisions to the diagnostic criteria for genetic mutation testing for early-onset bilateral sensorineural hearing loss, for which seven genes had been analyzed since 2018, we changed the specifications of the NGS panel test from October 2022 so that results for a total of 11 genes, including four newly added genes, would be reported.」

「Through collaboration with the Department of Artificial Hearing at the School of Medicine, Shinshu University, we had been upgrading the genetic mutation analysis test for congenital hearing loss. As planned, we upgraded the detection panel from 154 mutations in 19 genes to 1,135 mutations in 50 genes and began providing information on the switch to the new method from 20 September 2022. We also independently developed a research test measuring blood sitosterol, campesterol, and cholestanol by mass spectrometry (LC-MS/MS), and began offering it on a contract basis in October 2022.」

「We are incorporating part of this research test into the insurance-covered testing framework and upgrading the panel to detect 1,135 mutations in 35 genes, with preparations under way to begin offering it as a new contract test from September 2022.」

「As a result of research and development activity during the consolidated fiscal year, in the field of human genome analysis using NGS, genetic mutation analysis for familial hypercholesterolemia became eligible for insurance reimbursement of 5,000 points as one of the covered genetic tests under the April 2022 revision of medical reimbursement. In addition, in the field of hereditary connective tissue diseases (HCTD), we had been jointly developing a comprehensive genetic mutation detection panel with the Genetic Medicine Research Center at the School of Medicine, Shinshu University since the previous year. The panel analyzes 22 diseases and 52 genes by NGS, including seven diseases eligible for insurance coverage. As a result, in March 2022 we established a system for contract analysis at the BML General Research Laboratory.」

「Although infections appeared to have subsided last November, the spread of the sixth wave resumed from December, so we have restarted the L452R mutation screening test, which had been discontinued, to estimate the presence of the Omicron variant. We are also conducting full-genome viral sequencing using NGS to monitor the emergence and spread of new variants, and aim to establish a system capable of processing 1,000 specimens per day for this genomic analysis.」

「As most detected viruses have been replaced by the Delta variant and the spread of the fifth wave has subsided, the L452R mutation screening test that we have continued to conduct will end at the end of October. Going forward, full-genome viral sequencing using NGS will be required to monitor the emergence and spread of new variants. We have established a system capable of processing 500 specimens per day for this genomic analysis.」

「Beginning in the fourth quarter of the previous fiscal year, we collaborated with the National Institute of Infectious Diseases to launch N501Y mutation screening for all PCR-positive cases, contributing to government surveys monitoring the spread of the Alpha variant (UK variant). From the current fiscal year, we have continued L452R mutation screening to identify the Delta variant (Indian variant).」

「In addition, we began offering genetic analysis for spinocerebellar degeneration (SCD) on a contract basis in August of this year. Research into the disease mechanisms of spinocerebellar degeneration is currently advancing, and efficient genetic testing that helps provide accurate subtype diagnoses is needed to develop fundamental treatments. Following the test's eligibility for insurance coverage at 8,000 points as genetic testing, we redesigned the causal-gene analyses for the eight types previously offered individually—SCA1, SCA2, SCA3, SCA6, SCA8, SCA17, SCA31, and DRPLA—into a comprehensive test using multiplex PCR and Repeat Primed PCR that can analyze them all at once, and are offering it as a new proprietary test.」

「As a result of research and development activity during the first quarter, we began offering dystrophin gene mutation analysis using MLPA on a contract basis in April of this year. Muscular dystrophy, the target disease, is a general term for hereditary muscle diseases in which muscle fibers repeatedly undergo necrosis and regeneration, gradually atrophying as muscle strength declines. The disease is broadly classified into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is the severe form, involving complete absence of dystrophin, while BMD is the milder form, in which some function remains despite an incomplete deficiency. In recent years, gene therapies such as exon-skipping and read-through therapies for DMD have been established, and detailed analysis of dystrophin gene mutations is now required not only for diagnosis but also for treatment selection. This test is eligible for insurance coverage as genetic testing (D006-4), at 3,880 points.」

「As a result of research and development activity during the first nine months of the fiscal year, we began offering three proprietary tests on a contract basis. The first comprises LDLR gene mutation analysis using MLPA and single-site analysis of the FH gene using direct sequencing. We began offering these new tests in May 2019. The second is genetic analysis for congenital dyserythropoietic anemia (CDA). Through technical collaboration with the Department of Pediatrics at Nagoya University, we began offering genetic testing using next-generation sequencing (NGS), eligible for insurance coverage, on a contract basis in May 2019. The third comprises identification and monitoring tests for gene rearrangements used to measure minimal residual disease in bone marrow. In February 2019, we were accredited by the Japanese Society of Pediatric Hematology/Oncology as a facility eligible to perform this testing, and began general contract testing in June 2019 through collaboration with the National Hospital Organization Nagoya Medical Center.」

「As a result of research and development activity during the first six months of the fiscal year, we began offering three proprietary tests on a contract basis. The first comprises LDLR gene mutation analysis using MLPA and single-site analysis of the FH gene using direct sequencing. We began offering these new tests in May of this year, enabling us to provide information that supports early treatment and prevention of coronary artery disease by diagnosing FH and identifying carriers among patients' family members. The second is genetic analysis for congenital dyserythropoietic anemia (CDA). Through technical collaboration with the Department of Pediatrics at Nagoya University, we began offering genetic testing using next-generation sequencing (NGS), eligible for insurance coverage, on a contract basis in May of this year. The third comprises identification and monitoring tests for gene rearrangements used to measure minimal residual disease in bone marrow. In February of this year, we were accredited by the Japanese Society of Pediatric Hematology/Oncology as a facility eligible to perform this testing, and began general contract testing in June through collaboration with the National Hospital Organization Nagoya Medical Center.」

「There was progress in three major areas as a result of research and development activity during the consolidated fiscal year. The first was the ability to offer three new tests in the field of hematologic malignancies.」

「There was progress in three major areas as a result of research and development activity during the fiscal year. The first was NPM1 and KIT gene mutation analysis in connection with acute myeloid leukemia (AML) treatment. The launch of contract testing for these two new tests is expected to produce a certain degree of benefit in AML treatment. The second was genetic analysis for early-onset bilateral sensorineural hearing loss. Following the 2018 revision of medical reimbursement, the test became eligible for coverage as genetic testing for a designated intractable disease. Commercialization of this test was the first such achievement in Japan, and is expected to contribute to higher rates of genetic diagnosis and personalized medicine based on accurate diagnoses for patients with hearing loss. The third was MSI testing to determine eligibility for treatment with the anti-PD-1 antibody pembrolizumab (brand name: Keytruda). This test can be used to determine eligibility for the drug.」

「As a result of research and development activity during the first six months of the fiscal year, we newly began offering contract tests for NPM1 gene mutation analysis and KIT gene mutation analysis in connection with acute myeloid leukemia (AML) treatment.」

「As a result of research and development activity during the first quarter, we newly began offering contract tests for NPM1 gene mutation analysis and KIT gene mutation analysis in connection with acute myeloid leukemia (AML) treatment.」

「In the field of hematological diseases, we began contract testing in September of the same year for three new chimeric gene mRNA quantitative tests: DAZAP1/MEF2D, AML1/EVI1, and MLL/ELL. From October of the same year, we began contract testing for MPN genetic mutation analysis, which measures the three genes JAK2, MPL, and CALR as a set. In addition, recent reports have indicated that TLL1 gene polymorphisms are involved as a genetic factor in hepatocarcinogenesis after HCV eradication. As a new research test, we began offering TLL1 gene polymorphism analysis on a contract basis in December of the same year.」

「EGFR mutation analysis version 2.0, for which contract testing began last year, is intended to select patients eligible for osimertinib, a third-generation molecularly targeted therapy effective against lung cancer with the drug-resistance mutation T790M. From July this year, we expanded its application to cell-free DNA (cfDNA) specimens extracted from plasma and began offering it on a contract basis as a new companion test. We also began testing in September for ROS1 fusion gene mRNA to select lung cancer patients eligible for crizotinib. As genetic testing for intractable diseases, we began genetic analysis for fragile X syndrome and fragile X-associated disorders (FXTAS and FXPOI) in July, followed by genetic analysis for spinal muscular atrophy (SMA) in September. These were both the industry's first commercial contract-testing services. In the field of hematological diseases, we began contract testing in September for three new chimeric gene mRNA quantitative tests: DAZAP1/MEF2D, AML1/EVI1, and MLL/ELL. In nucleic acid testing for infectious diseases, we began offering a proprietary test for detecting herpesvirus-group nucleic acids on a contract basis in August. Using multiplex real-time PCR, this test enables the simultaneous quantification of six viruses as a set: HSV-1, HSV-2, VZV, EBV, CMV, and HHV-6.」

「In the field of hematological diseases, we began contract testing in January 2017 for minimal residual disease in multiple myeloma using eight-color multiparameter flow cytometry, the first such service in the industry. In transplantation medicine, we began contract testing in February 2017 for lymphocyte crossmatching by flow cytometry, which is more sensitive than the conventional cytotoxicity-based crossmatch test. In cancer diagnosis and treatment, we began contract testing in March 2017 for both PD-L1/22C3 and 28-8 immunohistochemical staining tests used to determine eligibility for immune checkpoint inhibitor treatment. In conjunction with this, we modified the existing MSI testing method used to diagnose Lynch syndrome, developed a new MSI test using five mononucleotide markers with paraffin-embedded pathological specimens as samples, and began offering it on a contract basis in March 2017.」

「There was also progress toward commercialization in the field of hematological diseases through the development of a new research test. The test measures blood L-asparaginase activity during induction and consolidation therapy for acute lymphoblastic leukemia. L-asparaginase is an essential component of the chemotherapy protocols used to treat this disease for many years. In cases where activity does not increase, the production of neutralizing antibodies is suspected, making the result an indicator for considering a review of the treatment protocol. The test will first be used on a trial basis in a clinical study conducted by the Japan Pediatric Leukemia/Lymphoma Study Group (JPLSG), where its usefulness and assessment criteria are scheduled to be evaluated and established.」

「In May 2016, we began performing EGFR mutation analysis version 2.0 using Roche diagnostic reagents on a contract basis. Following the first-generation molecularly targeted therapies gefitinib and erlotinib and the second-generation therapy afatinib for lung cancer, the new third-generation therapy osimertinib received marketing approval in March of the same year. This therapy is considered effective against lung cancer with T790M, a representative drug-resistance mutation, and EGFR mutation analysis version 2.0 was covered by national health insurance as a companion diagnostic used to confirm the presence or absence of this mutation and select patients eligible for osimertinib treatment.」

「In May 2016, we began performing EGFR mutation analysis version 2.0 using Roche diagnostic reagents on a contract basis. Following the first-generation molecularly targeted therapies gefitinib and erlotinib and the second-generation therapy afatinib for lung cancer, the new third-generation therapy osimertinib received marketing approval in March of the same year. This therapy is considered effective against lung cancer with T790M, a representative drug-resistance mutation, and EGFR mutation analysis version 2.0 was covered by national health insurance as a companion diagnostic used to confirm the presence or absence of this mutation and select patients eligible for osimertinib treatment.」

「In August 2015, we upgraded the genetic test for congenital hearing loss by using a next-generation sequencer (NGS) to substantially increase the number of genes analyzed to 19 and the number of mutations to 154, thereby improving the definitive diagnosis rate.」